Search

Pulmonary arterial hypertension (PAH) is characterized by persistent pulmonary vasoconstriction and pulmonary vascular remodeling. The pathogenic mechanisms of PAH remain to be fully clarified and measures of effective prevention are lacking. Recent studies; however, have indicated that epigenetic processes may exert pivotal influences on PAH pathogenesis. In this review, we summarize the latest research findings regarding epigenetic regulation in PAH, focusing on the roles of non-coding RNAs, histone modifications, ATP-dependent chromatin remodeling and DNA methylation, and discuss the potential of epigenetic-based therapies for PAH. [ABSTRACT FROM AUTHOR]

Functionalized graphene - metal nano-conjugates are used as Raman probes, in recent years, for trace level identification of materials having specific Raman active modes. In the present paper, model Raman probes were modeled through conjugation of Au and Ag clusters with functionalized graphene systems. In silico models of functionalized (5,5)-graphene sheets were designed at the density functional theory (DFT) level through attachments of epoxy, -OH and -NH(CH)SH/-CONH(CH)SH groups. Model Raman probes were designed through attachment of Au and Ag clusters to the functional sites. Full geometry optimizations followed by vibrational analysis were carried out to ensure that the designed Raman probes have acceptable geometric characteristics to attach Raman-active molecules to the metal site. Pyridine was used as a test system to investigate the functionality of such model Raman probes through attachment with the metal clusters. It was observed that the chemical effects due to such attachments increase the Raman intensities (RI) of specific Raman modes of pyridine (in-plane symmetric bending (1040 cm) and asymmetric stretch-bend (1634 cm)), which are too weak in the isolated molecule. Furthermore, the suggested in silico system could provide an important model for basic understanding of RI-enhancements of molecules through increase of the size of the metal clusters, as the observed enhancement was found to be dependent on the polarizability of the metal clusters attached to the molecule of interest. [ABSTRACT FROM AUTHOR]

Aims Establishment of an inflammatory milieu following elevated leukocyte adhesion to the vascular endothelium, which is mediated by transcriptional activation of cell adhesion molecules (CAMs), contributes to the pathogenesis of chronic hypoxia-induced pulmonary hypertension (HPH). The epigenetic switch that dictates CAM transactivation in response to hypoxia in endothelial cells leading up to HPH is not fully appreciated. Methods and results We report here that brahma-related gene 1 (Brg1) and brahma (Brm), two catalytic components of the mammalian chromatin remodelling complex, were induced in cultured endothelial cells challenged with hypoxia in vitro as well as in pulmonary arteries in an animal model of HPH. Over-expression of Brg1/Brm enhanced, while the depletion of Brg1/Brm attenuated, CAM transactivation and adhesion of leukocytes. Endothelial-specific deletion of Brg1/Brm ameliorated vascular inflammation and HPH in mice. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that hypoxia up-regulated the occupancies of Brg1 and Brm on CAM promoters in a nuclear factor κB (NF-κB) -dependent manner. Finally, Brg1 and Brm activated CAM transcription by altering the chromatin structure surrounding the CAM promoters. Conclusion Our data suggest that Brg1 provides the crucial epigenetic link to hypoxia-induced CAM induction and leukocyte adhesion that engenders endothelial malfunction and pathogenesis of HPH. As such, targeting Brg1 in endothelial cells may yield promising strategies in the intervention and/or prevention of HPH. [ABSTRACT FROM PUBLISHER]

Abstract: The activities of polyphenol oxidase (PPO) and pectin esterase (PE) in green eggplants during soaking treatments were analyzed to maintain the green color and improve the texture. The optimum temperature of PE was 65°C, but there was no significant difference from 50°C to 65°C, and PE activity could be enhanced by NaCl concentration (0.15–0.25M); the optimum pH of PPO was at 7.5, but inactivated when the pH was higher than 9.0; Enzymatic browning catalyzed by PPO could occurred when soaking temperature was higher than 55°C. The trials showed that response surface analysis (RSA) was a suitable method to optimize the soaking conditions. The soaking temperature and soaking time significantly influenced the texture of the green eggplant. Optimum texture (shear force value) was predicted and proved at the conditions of soaking temperature was 52.6°C, soaking time was 18.9min and the NaCl concentration was 0.224M. [Copyright &y& Elsevier]

Heterocyclic compounds occur widely in nature and in drug molecules. The activity of many nitrogen-containing heterocyclic compounds is unique. For example, 1,4-dihydropyridines display good antitumor and antibacterial effects and can be commercially used as calcium channel blocker agents in the treatment of cardiovascular diseases. To reduce the use of toxic catalysts in the synthesis of 1,4-dihydropyridines, here we designed cobalt carbon nanotubes as a heterogeneous catalyst. We report the efficient synthesis of 1,4-dihydropyridines under mild conditions, which allows to access a wide array of 1,4-dihydropyridines from aromatic aldehyde in high yields, up to 96%. Advantages include the use of ethanol as solvent, low catalyst loading of 6% mol, short reaction time of 5–15 min, easy preparation and recyclable catalyst. [ABSTRACT FROM AUTHOR]

Hypoxia induced pulmonary hypertension (HPH) represents a complex pathology that involves active vascular remodeling, loss of vascular tone, enhanced pulmonary inflammation, and increased deposition of extracellular matrix proteins. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator known to influence cellular response to stress signals in the vasculature. We report here that in response to chronic hypobaric hypoxia, MKL1 expression was up-regulated in the lungs in rats. Short hairpin RNA (shRNA) mediated depletion of MKL1 significantly ameliorated the elevation of pulmonary arterial pressure in vivo with a marked alleviation of vascular remodeling. MKL1 silencing also restored the expression of NO, a key vasoactive molecule necessary for the maintenance of vascular tone. In addition, hypoxia induced pulmonary inflammation was dampened in the absence of MKL1 as evidenced by normalized levels of pro-inflammatory cytokines and chemokines as well as reduced infiltration of pro-inflammatory immune cells in the lungs. Of note, MKL1 knockdown attenuated fibrogenesis in the lungs as indicated by picrosirius red staining. Finally, we demonstrate that MKL1 mediated transcriptional activation of type I collagen genes in smooth muscle cells under hypoxic conditions. In conclusion, we data highlight a previously unidentified role for MKL1 in the pathogenesis of HPH and as such lay down groundwork for future investigation and drug development. [ABSTRACT FROM AUTHOR]

Our previous studies revealed that the expression of stanniocalcin-1 (STC1) in astrocytes increased under hypoxic conditions. However, the role of STC1 in hypoxic astrocytes is not well understood. In this work, we first showed the increased expression of STC1 in astrocyte cell line and astrocytes in the brain tissues of mice after exposure to hypoxia. Then, we found that knockdown of STC1 inhibited cell viability and increased apoptosis. These effects were mediated by decreasing the levels of SIRT3, UCP2, and glycolytic genes and increasing the levels of ROS. Further studies suggested that STC1 silencing promoted oxidative stress and suppressed glycolysis by downregulating AMPKα1. Moreover, HIF-1α knockdown in hypoxic astrocytes led to decreased expression of STC1 and AMPKα1, indicating that the expression of STC1 was regulated by HIF-1α. In conclusion, our study showed that HIF-1α-induced STC1 could protect astrocytes from hypoxic damage by regulating glycolysis and redox homeostasis in an AMPKα1-dependent manner. [ABSTRACT FROM AUTHOR]

Evidence is mounting that sinomenine and peroxisome proliferator-activated receptor β/δ (PPARβ/δ) are effective against lipopolysaccharide (LPS)-induced acute lung injury (ALI) via anti-inflammatory properties. However, it is unknown whether PPARβ/δ plays a role in the protective effect of sinomenine on ALI. Here, we initially observed that preemptive administration of sinomenine markedly alleviated lung pathological changes, pulmonary edema and neutrophil infiltration, accompanied by inhibition of the expression of the pro-inflammatory cytokines Tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6), which were largely reversed following the addition of a PPARβ/δ antagonist. Subsequently, we also noticed that sinomenine upregulated adenosine A 2A receptor expression in a PPARβ/δ-dependent manner in LPS-stimulated bone marrow-derived macrophages (BMDMs). Further investigation indicated that PPARβ/δ directly bound to the functional peroxisome proliferator responsive element (PPRE) in the adenosine A 2A receptor gene promoter region to enhance the expression of the adenosine A 2A receptor. Sinomenine was identified as a PPARβ/δ agonist. It could bind with PPARβ/δ, and promote the nuclear translocation and transcriptional activity of PPARβ/δ. In addition, combined treatment with sinomenine and an adenosine A 2A receptor agonist exhibited synergistic effects and better protective roles than their single use against ALI. Taken together, our results reveal that sinomenine exerts advantageous effects on ALI by activating of PPARβ/δ, with the subsequent upregulation of adenosine A 2A receptor expression, and provide a novel and potential therapeutic application for ALI. [Display omitted] • SIN improves ALI effectively by inhibiting excessive inflammation in vivo and in vitro. • The protection of SIN may be mediated by the activation of PPARβ/δ-adenosine A 2A receptor pathway. • This study provided a theoretical basis for the clinical application of SIN. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) stimulates endothelin (ET-1) transcription, which contributes to cardiac hypertrophy and fibrosis. We have previously reported that myocardin related transcription factor A (MRTF-A) is indispensable for ET-1 transcription in vascular endothelial cells under hypoxic conditions, indicating that MRTF-A might mediate Ang II-induced pathological hypertrophy. Here we report that Ang II augmented the expression of MRTF-A in cultured endothelial cells and in the lungs of mice with cardiac hypertrophy. Over-expression of MRTF-A enhanced, whereas depletion of MRTF-A attenuated, transcriptional activation of ET-1 gene by Ang II. MRTF-A deficiency ameliorated Ang II induced cardiac hypertrophy and fibrosis in mice paralleling diminished synthesis and release of ET-1. Mechanistically, MRTF-A was recruited to the ET-1 promoter by c-Jun/c-Fos (AP-1) in response to Ang II treatment. Once bound, MRTF-A altered the chromatin structure by modulating histone acetylation and H3K4 methylation on the ET-1 promoter. More importantly, mice with endothelial-specific MRTF-A silencing by lentiviral particles phenocopied mice with systemic MRTF-A deletion in terms of Ang II-induced pathological hypertrophy. In conclusion, we data have unveiled a MRTF-A-containing complex that links ET-1 transactivation in endothelial cells to cardiac hypertrophy and fibrosis by Ang II. [ABSTRACT FROM AUTHOR]

The interaction between rice protein isolate (RPI) and ferulic acid (FA) was systematically investigated. The results showed that fluorescence intensity of the RPI decreased gradually upon increasing the concentration of ferulic acid, and the maximum emission shifted from 352.0 to 359.2 nm. It was proposed that a static quenching of RPI-FA complex occurred, due to the hydrophobic interactions. Moreover, CD spectra and FT-IR spectroscopy data suggested that the concentration of β-turn and α-helix decreased while those of random coil and β-sheet increased in RPI-FA complex. The decrease of intensity of the amide I band and amide II band in the RPI-FA complex implied a significant reduction of protein α-helical structure and the presence of non-polar hydrophobic interactions. In addition, SDS-PAGE results demonstrated that ferulic acid reacted with glutelin acidic subunits (34–37 KDa) as well as globulin (26 KDa), and ferulic acid might bind with aromatic amino acid residues of RPI. Furthermore, the RPI-FA complex exhibited high DPPH• scavenging ability, ABTS+• scavenging ability and ORAC value. Finally, emulsion stabilized by RPI-FA complex could decrease the concentration of hydroperoxide, TBARS, and hexanal, thereby effectively restraining fat oxidation degradation. Image 1 • Rice protein isolate and ferulic acid were interacted by hydrophobic interactions. • Ferulic acid reacted with gluten acid subunits and globulin of RPI. • RPI-FA complex could improve the oxidative stability of corn oil in emulsion. [ABSTRACT FROM AUTHOR]